Sequential hemibody irradiation integrated into a chemotherapy-local radiotherapy program for limited disease small cell lung cancer

Twenty-four patients with limited disease small cell lung cancer (SCLC) were treated with sequential hemibody irradiation (SHB) integrated into a conventional chemotherapy-local radiotherapy (LRT) program. Among 23 evaluable patients, 12 (52%) attained a complete response (CR) and 8 (35%) attained a partial response for an overall major response rate of 87%. The median time since study entry is 29 months. Durations of response are 9.9 months for all patients and 16.5 months for patients who achieved a CR. The primary site was the predominant area of recurrence. The median survival is 13.2 months for all patients and 23.2 months for the 12 patients who attained a CR. Myelosuppression, especially thrombocytopenia, was the major toxicity. Acute radiation toxicities and subacute pneumonitis previously associated with hemibody radiotherapy were well controlled or prevented using the current dose, premedication, and shielding techniques. This integrated program of systemic therapies with SHB and combination chemotherapy plus LRT is feasible for limited disease SCLC; it may prolong survival in patients who attain a CR but compared to similar programs without hemibody irradiation, there was no improvement in overall response rate, response duration, or survival.     

Combination chemotherapy with cisplatin and etoposide associated with radiotherapy in the treatment of small-cell lung cancer

Summary A total of 52 consecutive, previously untreated patients with small-cell lung cancer (SCLC) were scheduled to receive six cycles of a combination of etoposide (75 mg/m² per day) and cisplatin (20 mg/m² per day), each cycle given over 5 consecutive days. In all, 28 patients had extensive disease (ED) and 24, limited disease (LD). After three cycles of chemotherapy, all responding patients were given chest radiotherapy (RT) (45 Gy in two split courses and 30 Gy in LD and ED, respectively); only patients with LD who achieved complete remission (CR) after three cycles of chemotherapy were given prophylactic brain irradiation (30 Gy). In the 51 evaluable patients, the overall response rate was 90%, with a 31% CR and a 59% partial remission (PR) rate. In LD and ED patients, 57% and 11% CR rates and 30% and 82% PR rates were noted, respectively. Myelosuppression was the most frequently observed toxicity. The median duration of response was 12 months in LD (range, 3–41+months) and 7 months (range, 2–12 months) in ED; the median survival was 15 months in LD and 9.3 months in ED, respectively. In all 30% of LD patients are alive and well at a minimal follow-up of 18 months. This trial confirms the activity of the cisplatinetoposide combination in SCLC.Bursar, Italian Association for Cancer Research (AIRC)     

Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.

PURPOSE: The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS: One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS: A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION: The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.     

Prophylactic cranial irradiation in lung cancer

As multi-modality treatments are now able to ensure better local control and a lower rate of extra cranial metastases, brain relapse has become a major concern in lung cancer. As survival is poor after development of brain metastases in spite of specific treatment, prophylactic cranial irradiation (PCI) has been introduced in the 70's. PCI has been evaluated in randomized trials in both small-cell (SCLC) and non-small-cell (NSCLC) lung cancers to reduce the incidence of brain metastases and possibly increase survival. PCI reduces significantly the BM rate in both limited disease (LD) and extensive disease (ED) SCLC and in non-metastatic NSCLC. Considering SCLC, PCI significantly improves overall survival in LD (from 15% to 20% at 3 years) and ED (from 13% to 27% at 1 year) in patients who respond to first-line treatment; it should thus be part of the standard treatment in all responders in ED and in good responders in LD. No dose-effect relationship for PCI was demonstrated in LD SCLC patients so that the recommended dose is 25Gy in 10 fractions. In NSCLC, even if the risk of brain dissemination is lower than in SCLC, it has become a challenging issue. Studies have identified subgroups at higher risk of brain failure. There are more local treatment possibilities for NSCLC patients with BM, but most of them will eventually recur so that PCI should be reconsidered. Few randomized trials have been performed and they were not able to show an effect on survival as they were underpowered. New trials are needed.     

Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study

We designed an intensive, weekly treatment regimen for patients with small-cell lung cancer (SCLC) using six of the most active chemotherapeutic agents for this disease (doxorubicin [DOX], cyclophosphamide [CTX], vincristine [VCR], etoposide [VP-16], cisplatin [CDDP], and methotrexate [MTX]). The goal of this program was to gain rapid, repetitive exposure to multiple, active drugs. Treatment was administered weekly for a total of 16 weeks. Seventy-six SCLC patients (limited disease, 34; extensive disease, 42) were treated. The overall complete plus partial response rate was 82%. Complete response rates of 47% and 38% were observed in patients with limited (LD) and extensive disease (ED), respectively. The median survivals for patients with LD and ED were 16.6 and 11.4 months, respectively. Toxicities were tolerable and were primarily hematologic. Twenty-six patients had one or more transient life-threatening toxicities, but only one patient developed a fatal toxicity. Eighty-four percent of the patients received 80% or greater of the intended protocol dosages over the entire 16-week treatment period. We conclude that this intensive, short-duration treatment regimen is at least as good as other "standard" regimens, and we are encouraged aged by the complete response rate and median survival in patients with ED SCLC.     

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report

Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC).Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning.Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC.Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC.Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR >2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.     

Hemibody radiation, an active therapeutic modality for the management of patients with small cell lung cancer

In a previously published paper, the results of a preliminary clinical trial comparing systemic radiation (upper and lower hemibody technique) versus systemic chemotherapy in the management of all stages of small cell lung cancer (SCLC), suggested that hemibody radiation (HBI) was as efficient as systemic chemotherapy, particularly for patients with early disease. We are now presenting the final results of the above trial. The two year survival has shown that as many patients in the HBI as in the chemotherapy arm have reached this endpoint. However, there is a difference in favor of chemotherapy on both the median and one year survival for those patients with advanced stages. Therefore, as of June 1981, we have initiated a study incorporating HBI as a consolidating-maintenance agent for patients with all stages of the disease who have received a 3 1/2 months induction systemic chemotherapy plus local chest irradiation. Up to date, 65 patients have been entered and our median survival for those who received the complete treatment is 62.5 weeks.     

Progress in treatment of small-cell lung cancer: role of CPT-11

Small-cell lung cancer (SCLC) accounts for approximately 15% of all cases of lung cancer and is a particularly aggressive form of lung cancer characterised by a poor prognosis, rapid tumour growth, and early metastasis. Roughly, two-thirds of patients with SCLC present with extensive disease (ED) and one-third with limited disease (LD). Combination chemotherapy is the most effective treatment modality for SCLC, and several new agents, including carboplatin, ifosfamide, taxans, and topotecan, have been demonstrated to be active; however, there are no data on the survival benefit of these drugs. A CPT-11+ cisplatin regimen has shown improvement in overall survival over the global gold standard regimen, etoposide + cisplatin (Japanese Clinical Oncology Group: JCOG 9511), and three confirmatory randomised controlled trials are in progress to determine the reproducibility of the JCOG 9511 study. JCOG is evaluating the role of CPT-11 and a new triplet regimen containing CPT-11 in limited-stage SCLC. Strategies and the current protocols of the JCOG are presented and discussed. In the future, it will be essential to evaluate molecular target-based drugs for LD and ED SCLC with new standard combination chemotherapy regimens that include CPT-11.     

Characteristics, treatment patterns and outcomes of patients with small cell lung cancer—A retrospective single institution analysis

Purpose

The aim of this retrospective study is to present data on patient characteristics, treatment patterns, and treatment results in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).

Patients and methods

From June 2004 to December 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed lung cancer. 397 patients were found having SCLC. We collected data on patient characteristics, chemotherapy, side effects, response on treatment and survival.

Results

39% of all patients had LD SCLC. Median age was 63 years. The response rate (RR) reached 76%. Stable disease was the result of first line therapy in 16%. Consecutive thoracic radiotherapy was given in 72%. Additional prophylactic cranial irradiation (PCI) was administered to 33%. 43% received second line therapy. Median survival was 18.8 months.In 61% of cases, ED SCLC was diagnosed. Median age was 61 years. Main metastatic sites were liver, bone, brain and adrenal glands. RR was 69%. Stable disease and progressive disease were the result of first line chemotherapy both in 12%. 15% received palliative cranial irradiation, 3% PCI. 51% were treated with second line therapy. Median survival reached 10.6 months.

Conclusion

We provide a comprehensive analysis of a contemporary patient population. Treatment patterns and survival data fit well in the context of current international trials on more selected patients. Multivariate analyses confirmed extend of disease, performance status and LDH serum levels as independent prognostic factors for survival. Age and gender reached no statistical significance.     

Combined modality treatment of short duration in small cell lung cancer

Fifty-seven patients with small cell lung cancer (SCLC) (limited disease = LD in 23, extensive disease = ED in 34) received the combination of CCNU, cyclophosphamide, vincristine and methotrexate (CCOM). A mean number of only 6 (range 1–17) courses of chemotherapy were given. All LD patients received consolidation locoregional radiation (30 Gy) after two courses of chemotherapy. A complete response (CR) was obtained in 61% of LD and 12% of ED patients, and a partial response in 22 and 35% respectively. Median survival was 54 and 34 weeks for LD and ED respectively. Five LD patients survived more than 2 yr, three of them remaining disease-free 4 yr after the cessation of treatment. A subset of 12 LD patients achieving a CR after two courses of chemotherapy was randomized to receive maintenance chemotherapy or observation only after the consolidation radiotherapy. In this small-sized randomized trial maintenance treatment showed a significant decrease of the patients' quality of survival compared to no maintenance treatment. We conclude that combined modality treatment of short duration proved effective in SCLC. Future randomized studies are necessary to show whether prolonged chemotherapy has a meaningful impact on survival, or otherwise the resulting morbidity will plead against it.     

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.     

Prophylactic cranial irradiation in patients with small-cell lung cancer: the experience at the Institute of Oncology Ljubljana

Background

Prophylactic cranial irradiation (PCI) has been used in patients with small-cell lung cancer (SCLC) to reduce the incidence of brain metastases (BM) and thus increase overall survival. The aim of this retrospective study was to analyze the characteristics of patients with SCLC referred to the Institute of Oncology Ljubljana, their eligibility for PCI, patterns of dissemination, and survival.

Patients and methods

Medical charts of 357 patients with SCLC, referred to the Institute of Oncology Ljubljana between January 2004 and December 2006, were reviewed to determine characteristics of patients chosen for PCI. The following data were collected: age, gender, performance status (PS), extent of the disease, smoking status, type of primary treatment with outcome, haematological and biochemical parameters, PCI use, and finally brain metastases (BM) status at diagnoses and after treatment.

Results

PCI was performed in 24 (6.7%) of all patients. Six (25%) patients developed brain metastases after they were treated with PCI. Brain was the only site of metastases in 4 patients, two progressed to multiple organs. Median overall survival of patients with PCI was 21.9 months, without PCI 12.13 months (p = 0.004). From the collected data there were good prognostic factors: age under 65 years, limited disease (LD), performance status, normal levels of lactate dehydrogenase (LDH) and normal levels of C-reactive protein levels (CRP). Other prognostic factors did not show statistical significant values.

Conclusions

Survival of patients with LD, who have had PCI, was significantly better than those who had not. We decided to perform PCI in patients with LD, in those with complete or near complete response, and those with good performance status (≥ 80). We did not use PCI in extended disease (ED). The reason for that shall be addressed in the future. Doses for PCI were not uniform, therefore more standard approach should be considered.     

Progress in the management and outcome of small-cell lung cancer in a French region from 1981 to 1994

Recent analyses of series of small-cell lung cancer (SCLC) patients included in clinical trials have shown improved survival over time, but it has been impossible to determine whether this was due to selection biases, stage migration, or true therapeutic improvement. To determine if there has been a true improvement of survival over time, we reviewed the medical records of all consecutive patients diagnosed with SCLC between 1981 and 1994 in the Bas-Rhin in France. Among the 787 patients (median age 63), there was no significant period effect for sex, age, or stage. Staging work-ups became increasingly thorough (significant period effect). The mean number of investigations and of tumour sites detected correlated significantly. The chemotherapy rate increased (from 76.4% in 1981-1983 to 91.7% in 1993-1994, P = 10(-5)) and mediastinal irradiation decreased (to roughly 25% of patients after 1983). Median survival time increased for the overall population from 6.6 months in 1981-1983 to 11.3 months in 1993-1994 (P = 10(-5)), for patients with limited disease (LD) from 9.2 (P = 0.002) months to 14.0 months, and for those with extensive (ED) disease from 3.5 months to 9.6 months (P = 10(-5)). Significant independent prognostic factors were disease extent, clinical trial participation, period, type of chemotherapy, and mediastinal irradiation in LD. Survival time has truly improved as 'state of the art' management of SCLC has changed.     

Management of chemotherapy-related anaemia with low-dose recombinant human erythropoietin in patients with small cell lung cancer

We examined the efficacy of low-dose erythropoietin in the management of chemotherapy-related anaemia in patients with small cell lung cancer (SCLC). We gave recombinant human erythropoietin A (rHuEPO) to 63 SCLC patients, 30 with limited disease (LD) and 33 with extensive disease (ED) who underwent chemotherapy with carboplatin, etoposide and ifosfamide and had previously received blood transfusions for chemotherapy-related anaemia. rHuEPO was given at a dose of 2000 IU subcutaneously three times per week for 2 weeks after every chemotherapy cycle, starting 48 h after the end of chemotherapy. Before the use of rHuEPO, all patients in both groups had to be transfused after a mean of 5.5 CT cycles. In 64 CT cycles following administration of rHuEPO, only 5/30 LD patients (17%) had to be transfused in six cycles (9%). In 88 cycles following the use of rHuEPO, 7/33 ED patients (21%) had to be transfused in 11 cycles (12.5%). Haemoglobin values in patients with ED (but not those with LD) were significantly improved after rHuEPO administration on both day 14 and day 28 after chemotherapy. No adverse effects were recorded. rHuEPO considerably decreased the degree of anaemia and the need for blood transfusion at doses markedly lower (25–30 IU/kg body weight) than those reported in the literature so far (150 IU/kg body weight), without toxicity.     

Place actuelle de l’irradiation prophylactique cérébrale

Prophylactic cranial irradiation (PCI) plays a role in the management of lung cancer patients, especially small cell lung cancer (SCLC) patients. As multimodality treatments are now able to ensure better local control and a lower rate of extracranial metastases, brain relapse has become a major concern in lung cancer. As survival is poor after development of brain metastases (BM) in spite of specific treatment, PCI has been introduced in the 1970's. PCI has been evaluated in randomized trials in both SCLC and non-small cell lung cancer (NSCLC) to reduce the incidence of BM and possibly increase survival. PCI reduces significantly the BM rate in both limited disease (LD) and extensive disease (ED) SCLC and in non-metastatic NSCLC. Considering SCLC, PCI significantly improves overall survival in LD (from 15 to 20% at 3 years) and ED (from 13 to 27% at 1 year) in patients who respond to first-line treatment; it should thus be part of the standard treatment in all responders in ED and in good responders in LD. No dose-effect relationship for PCI was demonstrated in LD SCLC patients so that the recommended dose is 25 Gy in 10 fractions. In NSCLC, even if the risk of brain dissemination is lower than in SCLC, it has become a challenging issue. Studies have identified subgroups at higher risk of brain failure. There are more local treatment possibilities for BM related to NSCLC, but most BM will eventually recur so that PCI should be reconsidered. Few randomized trials have been performed. Most of them could demonstrate a decreased incidence of BM in patients with PCI, but they were not able to show an effect on survival as they were underpowered. New trials are needed. Among long-term survivors, neuro-cognitive toxicity may be observed. Several approaches are being evaluated to reduce this possible toxicity. PCI has no place for other solid tumours at risk such as HER2+ breast cancer patients.     

Phase II trial of the combination of carboplatin and irinotecan in elderly patients with small-cell lung cancer

Aim

The aim of the present phase II study was to assess the antitumour activity and safety of the combination of irinotecan and carboplatin in elderly patients with small-cell lung cancer (SCLC).

Material and methods

Patients with previously untreated SCLC were eligible if they had a performance status of 0-2, were 70 years or older, and had adequate organ function. Patients were treated with carboplatin at an area under the plasma concentration versus time curve of 5 min/ml on day 1 and with irinotecan at 50 mg/m² on days 1 and 8 every 3 weeks.

Results

Thirty patients (26 men and 4 women; median age, 76 years; age range, 70-86 years) were enrolled. Eight patients had limited disease (LD) and 22 patients had extensive disease (ED). The overall response rate was 83.3% (95% confidence interval: 65.3-94.4%). Response rates did not differ significantly between patients with LD (87.5%) and those with ED (81.8%; p = 0.71). The median survival time was 14 months overall and was significantly longer in patients with LD (26 months) than in patients with ED (11 months; p = 0.025). The median progression free survival time was 6 months overall and was significantly longer in patients with LD (12 months) than in patients with ED (6 months; p = 0.016). Grade 3-4 toxicities included neutropenia in 83% of patients, thrombocytopenia in 47%, anaemia in 60%, infection in 23%, and diarrhoea in 20%. There were no treatment-related deaths.

Conclusions

This chemotherapy is safe and effective for elderly patients with SCLC.     

Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P=0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P=0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.     

A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactiv whole brain irradiation

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.     

Flow cytometric analysis of tumor DNA profile related to response to treatment and survival in small-cell lung cancer

Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has been widely used to predict prognosis and treatment response in many malignant tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of 36 small-cell lung cancer patients treated with combination chemotherapy and radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a statistically non-significant trend towards more aneuploidy among extensive disease (ED) patients as compared to patients with limited disease (LD): 80% versus 65%, respectively (p = 0.69). The mean SPF was 213% (± 7.6) in patients with LD and 29.0% (± 5.3) in patients with ED, the difference (7.6%) being statistically significant(p = 0.008, 95% CI for the difference 2.2-13.1). No significant differences was detected in the survival of aneuploid and diploid patients or patients with low (⩽24.9%) and high (>24.9%) SPF. Similarly, no significant difference was observed between aneuploid and diploid cases in relation to response to treatment or response duration. It is concluded that the difference detected in the SPF with LD and ED of SCLC may indicate the biological aggressiveness of extensive SCLC.     

The Role of Integrated 18F-FDG PET-CT as a Staging Tool for Limited-Stage Small Cell Lung Cancer: A Retrospective Study

Background: The aim of this study was to evaluate whether positron emission tomography-computed tomography (PET-CT) could be used as part of the staging work-up in patients with limited-stage disease (LD) small cell lung cancer (SCLC). Patients and Methods: Between January 2002 and December 2007, a total of 73 patients with presumed LD on CT, who underwent a PET-CT scan, were included in this study. Results: Conventional work-up revealed distant metastases in 12 patients. Out of 61 patients diagnosed as LD SCLC, PET-CT found unexpected distant metastases in 15 (24.6%) patients (LD/extensive-stage disease (ED)) of whom 13 (21.3%) were upstaged as a consequence. In 10 (76.9%) of the 13 upstaged patients, treatment was changed. The median survival of LD/LD SCLC patients who underwent concurrent chemoradiotherapy and chemotherapy only was 21.9 and 17.5 months, respectively. The median survival of LD/ED and ED/ED SCLC patients who received chemotherapy only was 17.4 and 14.1 months, respectively. The median survival of LD/LD SCLC patients who received concurrent chemoradiotherapy was superior to that of LD/ ED and ED/ED patients who received chemotherapy only (p = 0.037 and 0.004, respectively). Conclusion: The addition of PET-CT seems to allow more accurate staging and may thus protect a percentage of SCLC patients from potentially futile and toxic radiotherapy.